Oral Bisphosphonates Linked to 6-Fold Increase in Risk for Osteonecrosis of the Jaw

To lower risk for osteonecrosis of the jaw and other serious adverse effects, guidelines recommend a drug holiday in women who have had long-term use of bisphosphonates.

The use of oral bisphosphonates is associated with a 6-fold increased risk for hospital admission with osteonecrosis of the jaw in postmenopausal women, according to study results published in Bone.

Epidemiologic evidence for osteonecrosis of the jaw as an adverse effect of oral bisphosphonates is lacking. Researchers examined the incidence of hospital admission with osteonecrosis of the jaw in participants from the Million Women Study (n = 521,695). They used Cox proportional hazards regression to estimate adjusted relative risks and 95% CIs associated with the use of oral bisphosphonates in postmenopausal women.

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Participants’ mean age was 64.7 years at baseline. During a mean follow-up of 8.2 years per woman, 100 women were admitted to the hospital with first recorded osteonecrosis of the jaw. Of these women, 29 had used oral bisphosphonates.

The researchers determined that users of oral bisphosphonates had a 6-fold increased risk for hospital admission for osteonecrosis of the jaw compared with never-users (adjusted relative risk, 6.09; 95% CI, 3.83-9.66; P <.0001). The results also indicated that women who were never-users of oral bisphosphonates but had prior cancer had a relative risk of 3.40 (95% CI, 2.22-5.22; P <.0001).

The researchers calculated that the estimated absolute risk for hospital admission for osteonecrosis of the jaw during a 5-year period from age 70 to 74 years was 0.09/1000 for never-users with no history of cancer and 0.69/1000 for ever-users of oral bisphosphonates.

“To limit the possibility of serious side effects, recent guidelines in the UK suggest that long-term bisphosphonate therapy in postmenopausal women should be reviewed after about [3 to 5] years and that a drug holiday should be considered in women without a fracture with a score below the National Osteoporosis Guideline Group intervention threshold,” the researchers wrote.